The objective of this proposal is to identify and examine the cellular processes involved in the synchronization of neuronal activity in the hippocampus. Synchronized discharge consisting of the simultaneous burst firing of a large population of neurons can be readily recorded in the hippocampal slice when the GABAergic synaptic inhibition is blocked by convulsive agents. We have previously identified two processes important in the initiation of synchronized discharge. These are (1) the intrinsic bursting capability of the dendrites and somata of hippocampal pyramidal cells and (2) the reciprocal excitatory synaptic connection between these cells. The immediate objectives of the proposed study are: (1) To analyze the kinetic and pharmacological properties of voltage-dependent ionic channels in the hippocampal pyramidal cell. We will begin by studying the non-inactivating inward current presumed to be important in sustaining burst firing. (2) To examine the anatomical and physiological properties of the recurrent synaptic network within a population of synchronized neurons. We will carry out the study with two experimental approaches. This includes the hippocampal slice preparation and our recently developed dissociated cell preparation. Our preliminary data show that viable, dissociated pyramidal cells can be obtained from adult guinea pigs. In addition we have demonstrated that voltage-clamp analysis of macroscopic membrane currents and patch-clamp approach for single-channel current studies can be carried out using dissociated cells. These technical advances have made it possible to begin a quantitative analysis on the membrane and receptor properties of hippocampal cells. We will use these data to coroborate those derived from the slice preparation to provide a better understanding of the synchronization process. Since the convulsant-induced synchronized discharge that we record in the hippocampus slice can be compared directly to the interictal spikes recorded by electroencephalograph in epilepsy, the results of our study may also contribute to our understanding of the initiation and control of interictal spikes in the diseased brain.